Inflammation is usually beneficial

Question 1

What is inflammation?

Answer 1

It is the tissue response to injury or infection, characterised by an increase in blood flow, swelling, elevated temperature, pain and redness.

Question 2

Name a key component of inflammation

Answer 2

The complement system

Question 3

What is the complement system?

Answer 3

A set of ~20 or more different proteins which act in an enzymic amplification cascade system to generate a number of active complement components (small signal, large response) involved in several aspects of the immune response. These are soluble molecules released by cells and receptors.

Question 4

Where is the complement system synthesised?

Answer 4

By the liver and macrophages (the main two)

Question 5

What is a zynogen?

Answer 5

An inactive form of an enzyme which can be cleaved and split to form the active form of the enzyme.

Question 6

What are the three complement pathways?

Answer 6

Classical, lectin and Alternative

Question 7

Which are the two most similar complement pathways?

Answer 7

Classical and lectin

Question 8

How is the classical pathway activated?

Answer 8

By immune complexes Ab-Ag

Question 9

What is C1-INH

Answer 9

It is the complement component c1 inhibitor which regulates the activation of c1.

Question 10

Which component of the classical and lectin pathway has C3 convertase activity?

Answer 10

C4b2a

Question 11

Which component of the classical and lectin pathway has C5 convertase activity?

Answer 11

C4b2a3b

Question 12

What is the common end point of the classical and lectin pathway?

Answer 12

C5 is splitting into C5a and C5b. C5b then binds to C6-9 to form the membrane attack complex (MAC)

Question 13

How does the lectin pathway differ from the classical?

Answer 13

The lectin pathway is activated by surface carbohydrates of bacterial cell walls. Lectin is a protein that binds carbohydrates. An example of a lectin is mannose binding lectin (MBL).

Question 14

How is the alternative pathway activated?

Answer 14

by components of microbial cell surfaces, not carbohydrates, more protein based.

Question 15

Which component of the alternative pathway has C3 convertase activity?

Answer 15

C3bBb

Question 16

Which component of the alternative pathway has C5 convertase activity?

Answer 16

C3bBb3b

Question 17

What is the universal common stage of complement activation?

Answer 17

The splitting of C3 into C3a and C3b.

Question 18

What binds to C3b to give it it’s C3 convertase activity?

Answer 18

factor B

Question 19

True or false: components of the complement system before the cleavage of C3 have immunological or physiological activity?

Answer 19

False, they no not have these activities until C3 is cleaved. Autocatalysis of C3 occurs minimally.

Question 20

Which complement components are involved in immune responses?

Answer 20

C3a, C3b, C5a and MAC. These are not present in high levels where there is not an infection but are amplified in infection.

Question 21

Which complement components stimulate mast cells?

Answer 21

C3a, C5a and C4a (Former two more so), mast cells are located in mucosal and connective tissue and release granules (degranulation) containing inflammatory mediators.

Question 22

What does C5a do?

Answer 22

neutrophil chemotaxis

Question 23

What does C3b and C4b do?

Answer 23

opsonisation (decreasing the likelihood of no recognition of the pathogen), C3b also clears immune complexes

Question 24

What does C5b-C9

Answer 24

cell lysis (MAC)

Question 25

What does C3d do?

Answer 25

B-cell activation, arises from C3a and C3b splitting.

Question 26

How do our own cells prevent against the harmful effects of complement?

Answer 26

Through the expression of surface inhibitory proteins CD55 and CD59

Question 27

How does the MAC operate?

Answer 27

Produces lytic complex on microbial cell membranes; deposition of C5 convertase on pathogen surface, C3bBb3b (or equivalent in classical/lectin) cleaves C5. C5b remains on cell surface. C6 and 7 insert partly into membrane. C8 penetrates cell membrane. C5b+6+7+8 act as catalysts for the polymerisation of several different C9 molecules which will insert into the membrane and polymerise to forma pore like strucuture inducing osmotic shock.

Question 28

What does inflammation involve?

Answer 28

inflammatory mediators released from tissue mast cells (degranulation via PAMPs/tissue damage and becomes activated.

Question 29

What are the two outcomes of mast cell activation?

Answer 29

i) release of granules to outside of mast cells; degranulation. Granules contain vasoactive amines (histamine), cytokines and chemokines.
ii) Activation of enzymes; Phospholipase A2 activation-Arachidonic acid pathway of 2 subpaths;
1) Lipoxygenase pathway resulting in leukotrienes; inflammatory mediators
2) cyclo-oxygenase pathway = prostaglandins - inflammatory mediators.

Question 30

Describe the process of extrovasion of neutrophils;

Answer 30

Chemotaxis of circulating cells to infected tissues; neutrophils are the main cell (70%) and attracted by C5a. Enhanced vascular permeability facilitates chemotaxis. Neutrophils adhere to vascular endothelium through adhesion molecules such as E-selectin on endothelium binding to CD15 on neutrophils (glycosylated transmembrane adhesion proteins) causing rolling along blood vessel wall and induces expression of other adhesins; integrins of neutrophils which binds to ICAM-1 also has induced expression by LPS, TNF, IL-1 (positive feedback). In response to activating substances released by infectious agent and damage tissue causes E-selectin production. Once adhesion is achieved, diapedesis through the vascular endothelium and basement membrane occur; access to infection site.